BACKGROUND
AND OBJECTIVES: The number of new users of illicit substances has been growing
steadily all over the world over the last few years. Marijuana and cocaine have
been mentioned most often, but the last few years saw a marked increase in the
number of users of other psychostimulants or hallucinogens, taken with the aim
of intensifying social experiences. The aim of this article is to discuss the
clinical presentation, the damaging effects and the potential interactions with
anesthesia of the surgical patient who is a user of these illicit substances.CONTENTS: The article discusses the action mechanisms, the clinical presentation,
the damaging effects and the potential repercussions observed during anesthesia
in users of MDMA (3,4-methylenedioxymethamphetamine), also known as Ecstasy.CONCLUSIONS: Anesthesiologists should be made aware of the clinical presentation
and the damaging effects brought about by 3,4 - methylenedioxymethamphetamine
(Ecstasy), as well as the potential interactions with anesthesia, since people
who use these substances may find themselves in surgery many times, either due
to an emergency situation or by choice.

The
number of new users of illicit substances has been growing steadily all over the
world over the last few years. In the United States, there were approximately
19 million people over the age of 12 using illicit drugs in 2003, that is, 8.2%
of the country's population. Marijuana and cocaine has been mentioned most often,
but the last few years a new market has increased in the number of users of other
psychostimulants or hallucinogens, taken with the aim of intensifying social experiences.
As these are often found in night clubs, raves or parties playing electronic music,
these drugs are generically referred to as Club Drugs. Substances such as 3,4-methylenedioxymethamphetamine
(MDMA), commonly called Ecstasy, gamma-hydroxybutyrate (GHB), flunitrazepam
(Rohypnol®), ketamine (Ketalar®), methamphetamine
e lysergic acid (LSD) are the main substances that make up this group 2
(Chart I). According to Demetriades et al. 3
in a study conducted at the University of Southern California, 53% of patients
with fire gun wounds, 33% of victims of car accidents and 29% of people hit by
cars tested positive for alcohol and/or illicit drugs. Hence, anesthesiologists
should be made aware of the clinical conditions and the damaging effects that
these psychostimulant and hallucinogenic substances have on the body, since there
may be many situations in which users of such substances need to be given an anesthetic.

DEVELOPMENT

The
synthetically produced amphetamine MDMA, also known as Ecstasy, is a compound
with hallucinogenic and stimulant properties on the central nervous system 4.
There are two other substances with similar pharmacological properties that can
be found in the black market: N-ethyl-3,4 methylenedioxyamphetamine, popularly
referred to as Eve, and MDMA's active metabolite 3,4-methylenedioxyamphetamine
or MDA. In 2003, it was estimated that 2.1 million Americans over the age of 12
(0.9%) had taken Ecstasy at least once during the year course prior to
when the research was conducted 5. In Brazil, according to a national
survey on the use of psychoactive substances, approximately 0.6% of the people
interviewed over the age of 12 reported that they had taken Ecstasy6
or another hallucinogen at least once in their lives and there are evidences that
the number of users grows with each passing year 7,8.

MDMA
was manufactured and patented by the pharmaceutical company Merck in 1912 as an
appetite suppresant, but it was found to not be commercially feasible. In the
1950's, it was once again released as a way of decreasing the inhibition of patients
undergoing psychoanalysis 9. In 1985 it was officially declared illegal
for any use in the United States, as its employ as a recreational drug was already
rampant. This was also the case in Europe, where Ecstasy had never been
considered legal. Although there are indications that the chronic use of MDMA
causes lesions in the serotoninergic neurons, limitations involving the methodology
of studies conducted so far do not allow for a definite conclusion regarding the
toxicity of this substance to human beings 10 .

MDMA
is taken orally and is found in pill form or in capsules in a variety of colors
and sizes. As it is a drug produced illegally, there is no control over the composition
of the pills, which may contain a large variety of substances such as methylenedioxyamphetamine
(a toxic metabolite of MDMA), caffeine, atropine, ketamina, ephedrine, diphenhydramine,
amphetamine and methamphetamine11. Ecstasy begins to take effect
approximately 20 minutes after the user ingests the pill and its duration varies
from 4 to 8 hours. Despite uncertainty regarding the pills' composition, studies
involving the effect caused by different makes of Ecstasy appear to have
the same effects 12-14.

A
single mechanism is probably not enough to explain the effects induced by MDMA.
The complex spectrum of its activity on the human behavior suggests that the effects
produced by the consumption of this substance are a result of multiple neurochemical
processes involving serotonin, dopamine and noradrenaline, which makes it similar
to the other amphetamines 13.

According
to de Almeida et al. 14, in a research project conducted in São
Paulo, users of MDMA described the sensation as happiness, energy, peace, euphoria,
"having an open mind," "lacking in worries" and "having a sense of calmness."
An important piece of information obtained in this study was that many users reported
that they also consumed other illicit substances in addition to Ecstasy,
such as marijuana, lysergic acid (LSD) and cocaine, as well as tobacco and alcohol.
Chart II summarizes the possible adverse reactions, as
well as the neurological mechanisms that are probably involved.

Hyperthermia
induced by MDMA has been reported in humans 15,16 and observed in studies
conducted on animals of different species.

According
to Fiege et al. 17, malignant hyperthermia was induced in pigs that
were genetically susceptible to this syndrome after having been exposed to high
doses of MDMA. However, the use of dantrolene, which is employed in the treatment
of malignant hyperthermia, has not proved effective in controlling the thermogenic
effects induced by MDMA, suggesting there is another mechanism involved in this
complicated picture 18. Some authors are suggesting that the drug induces
a large amount of serotonine to be released from the serotoninergic nerve terminals,
which in turn is responsible for the group of symptoms that include hyperthermia
(body temperature of up to 42 ºC), altered mental states, hemodynamic instability,
muscular hypertonia, rhabdomyolysis, and kidney and cardiac failure19.

Cases
have also been registered of seizures supposedly caused by hyponatremia and by
brain edema, that in turn were probably brought about by water intoxication as
a result of the excessive water intake in people with heavy sweating provoked
by the increase in body temperature induced by MDMA and aggravated by the intense
physical activity expended during parties with electronic music 20.
Hepatic lesion was determined among the first registered cases of death due to
MDMA abuse in the United Kingdom and it appeared to have been a result of hyperthermia
or disseminated intravascular coagulation 21. Reneman et al. 22
found that users of MDMA had a predisposition towards cerebral vascular accidents.
The chronic use of the substance may trigger memory dysfunction, changes in cognitive
abilities and in behavior as a consequence of the lesions caused by the serotoninergic
neurons on the central nervous system 23.

The
treatment for MDMA intoxication should be fast and efficient, since complications
tend to increase in number and degree of gravity if this is not the case. Certain
support measures should also be included, such as: maintaining the permeability
of the respiratory tract, ventilatory support, supplying the patient with 100%
oxygen, maintaining urinary output and supplying cold fluids (via the stomach,
gall bladder and veins) in cases of hyperthermia. The increase in temperature
should be treated with urgency, since untreated cases may result in rhabdomyolysis
and disseminated intravascular coagulation 24-26. Although dantrolene
is recommended as a treatment option, in cases of hyperthermia induced by MDMA,
there is little evidence in the literature supporting its effectiveness 11.
Hydration and electrolyte reposition should be undertaken with caution in patients
with suspected hyponatremia and water intoxication 1.

A
neuromuscular blocker should be employed in cases where there is muscular rigidity
induced by the excessive release of serotonin on the central nervous system. High
blood pressure should be treated with sodium nitroprussiate, phentolamine or with
labetalol. You should avoid using b-blockers employed
with previously administering a1 blocking
agents in patients with symptoms suggesting MDMA intoxication 27. Vasoconstrictors
should be applied with caution in patients who are Ecstasy users, even
when the spinal block leads to low blood pressure, because this association commonly
results in sympathetic hyperactivity 28.

CONCLUSION

Illicit
substance abuse is one of the largest public health concerns the world is facing.
Marijuana and cocaine are the most commonly used substances, but the last few
years has seen a steady increase in the number of users of other psychostimulants
and/or hallucinogens, such as MDMA (also known as Ecstasy), which is associated
to countless adverse reactions. Anesthesiologists should be made aware of the
clinical presentation and the damaging effects brought about by this drug, as
well as the potential interactions with the anesthesia, since people who use these
substances will often find themselves in surgery, either due to an emergency situation
or elective.